Safety, mucosal and systemic immunopotency of an aerosolized adenovirus-vectored vaccine against SARS-CoV-2 in rhesus macaques

Abstract

Mucosal immunity provides a potential for preventing initial infection and stopping subsequent transmission of SARS-CoV-2. Here, we examined the safety and immunogenicity of a replication-defective adenovirus type-5 vectored vaccine (Ad5-nCov) encoding SARS-CoV-2 spike protein delivered by nebulization inhalation in rhesus macaques. The vaccine-associated clinical pathology and toxicity were not observed in the NHP model. The extensive safety study indicated that Ad5-nCoV was mainly confined to the organs related to respiratory system and was rapidly cleared away from the system. Our results showed that Ad5-nCoV delivered by inhalation robustly elicited both systematic and mucosal immune responses against SARS-nCoV-2 and variants. Thus, Ad5-nCoV inhalation may provide an effective, safe and non-invasive vaccination strategy for the control of SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2 vaccine; aerosol; immunoglobulin A; inhalation; mucosal immunity; safety.

Figure 1.

Safety and immunogenicity of aerosol Ad5-nCoV. (A) Biodistribution of Ad5-nCoV in the tested organs collected on 31 and 42 DPI. The viral genome in the tissues was assessed with qRT-PCR. (B) Ad5-nCoV presence in the blood at the indicated time points. (C and D) S-specific humoral immune responses in serum and bronchoalveolar lavage. (E and F) Pseudovirus neutralization antibody (PNAb) titres for SARS-CoV-2 WT or Delta variant were elevated in blood and BLA, respectively. ****P < 0.0001, ***P < 0.001.